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Glucocorticoid effects on bone: The role of the osteoblast

Summary

 Glucocorticoid effects on bone: The role of the osteoblast

Supervisors

Professor Markus Seibel, Professor Hong Zhou.

Research location

Concord - ANZAC Research Institute

Program type

Masters/PHD

Synopsis

Background: Glucocorticoids (GCs) have both catabolic and anabolic effects on bone cells. However, the precise mechanisms of these seemingly disparate actions and their phenotypic consequences - bone loss and osteoporosis on the one side versus osteoblast differentiation on the other side - are still poorly understood. Using a transgenic mouse model of osteoblast-targeted pre-receptor disruption of GC-signalling we have recently made three key discoveries: firstly, mature osteoblasts direct mesenchymal progenitor (MP) cell lineage commitment; secondly, this control is achieved through the secretion of soluble signalling molecules by the osteoblast; thirdly, the secretion of these mediators is regulated by GCs acting on the mature osteoblast. Project hypothesis: GCs govern MP cell lineage commitment by regulating the expression of Wnt proteins in mature osteoblasts through transcriptional control. Project aims:

  1. Establish the role of Wnt/-catenin signalling in MP cell lineage commitment.
  2. Determine if GCs directly control Wnt gene transcription in mature osteoblasts.
  3. Determine if GCs interact with other transcriptional factors to regulate Wnt gene transcription in osteoblasts.

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Opportunity ID

The opportunity ID for this research opportunity is 252